Endogenous estrogens fall dramatically after natural or surgical menopause, and this decline results in a marked increase in bone loss and subsequent fractures. Endogenous estrogens are clearly important for the maintenance of skeletal health in younger women. However, the importance of endogenous estrogens in older women is less certain.
It has been previously shown that endogenous estrone levels in women over age 65 were not associated with subsequent hip or vertebral fractures. S. R. Cummings, et al., J. Bone Min. Res. 10 (Suppl I):S174 (1995). However, estradiol is a more potent estrogen that estrone, and studies of its relationship to fractures have been inconclusive. Serum estradiol levels in premenopausal women average over 100 pg/ml. Serum estradiol levels in postmenopausal women not being treated with hormone replacement therapy fall below 20 pg/ml and as many as 30-50 percent of postmenopausal women have serum estradiol levels which are undetectable by conventional, sensitive assay methods (i.e., less than 5 pg/ml). Conventional treatment for postmenopausal women includes estrogen replacement therapy in doses sufficient to maintain serum estradiol levels above 40-60 pg/ml.
Conventional hormone replacement therapy has proven useful for treating physical conditions resulting from postmenopausal estrogen decline, including reducing the loss of, or even increasing bone density; and decreasing the risk of bone fracture. However, studies have indicated that hormone replacement therapy may be linked to increased risk of breast and endometrial cancers, as well as blood clotting and bleeding from the uterus. Accordingly, there remains a need in the art for methods of treating the physical conditions which result from postmenopausal estrogen decline or deficiency. There also remains a need in the art for treating such physical conditions while reducing the side effects of hormone replacement therapy.